High performance liquid chromatography (HPLC) demonstrated advantages over conventional procedures employed in newborn and adult hemoglobinopathy screening programs for the identification of Hb variants has promoted the need to reassess our knowledge of hemoglobin reference ranges as it relates to HPLC quantitation. In this study, the HPLC hemoglobin reference ranges derived from 200 normal African American adults are expressed as follows: Hb A mean 93.6 percent (s.d. 1.3, ranges 89.8 to 95.2), Hb A1 mean 2.0 percent (s.d. 0.6, ranges 0.8 to 5.2), Hb F mean 3.2 percent (s.d. 0.7, ranges 1.7 to 5.3) and Hb A2 mean 1.2 percent (s.d. 0.4, ranges 0.5 to 3.4); while the HPLC results for normal newborns and babies (n = 99) in the African American population fluctuates from Hb F mean 82.0 percent (s.d. 7.7, range 66.6 to 89.9) and Hb A mean 19.0 percent (s.d. 7.7, ranges 10.1 to 33.4) at 4 days to a mean of 15. percent (s.d. 4.8, range 9.3 to 22.8) for Hb F and a mean of 85.0 percent (s.d. 5.1, ranges 76.4 to 90.7) for Hb A at 300 days after birth. In case of the most common hemoglobin variants for this population, it has been shown that the A/S and A/C ratios for adults (Hb AS, Hb AC) and newborns (Hb FAS, and FAC) remained within the 1.5 (range 1.0 to 2.2) limits regardless of age group. Application of these HPLC ranges to confront other abnormalities will prove most useful during blood screening processes.